An entirely new successful approach was used to prepare human P450 antigens by expression with baculovirus. Some of the antibodies showed inhibitory activity toward the respective P450. Antibody reactivity was screened by binding or Western blot analysis using vaccinia expressed P450. A lymphoblastoid cell line was also used to express P450s which was used to measure their mutagen activation activity. Monoclonal antibodies prepared to different forms of cytochrome P450 3A4 and 2E1 were used to determine the contribution of individual P450s to the metabolism of different carcinogenic and noncarcinogenic substrates. These include the esophageal carcinogen benzo[a]pyrene, taxol, testosterone, cyclosporin, phenanthrene, diazepam, sterigmatocystin, and p-Nitrosonornicotine.